Poor pregnancy outcomes and complications such as low birthweight, preeclampsia, prematurity, and gestational diabetes continue to be a significant problem in the United States, particularly for women who are members of ethnic minorities. Psychosocial factors contribute to poor pregnancy outcomes, and proinflammatory aspects of the immune system may be involved in these effects. Although work in our laboratory and others supports connections between prenatal stress and poor outcome, the mechanisms of these relationships remain unclear. We hypothesize that that prenatal maternal stress and low social support increase levels of proinflammatory cytokines during pregnancy and that these changes increase the probability of poor pregnancy outcomes. The proposed R21 project extends our preliminary data, which suggests that high stress during pregnancy is related to elevated proinflammatory cytokines and poor outcome, perform comprehensive analyses of the effects of stress on cytokines during pregnancy, to add assessment of the role of social support in this relationship, and to determine the degree to which these changes can be used to make clinically useful predictions of at-risk pregnancies. An important aspect of this project is that we will study an ethnically diverse population (predominately Caucasian women and Latinas) which will extend the usefulness of the work in developing understanding of ethnic disparities in these relationships. This R21 project tests the hypothesis that high stress and low social support increase maternal production of proinflammatory cytokines during pregnancy (Specific Aim 1) and that this increased production is associated with pregnancy complications and poor outcome (Specific Aim 2). Further, a mathematical modeling approach is proposed to begin to determine the possible clinical usefulness of cytokine levels and stress in identifying pregnancies that are at risk for poor outcomes (Specific Aim 3). An additional aspect of the project is beginning to assess the role of maternal ethnicity in these interactions to explore biobehavioral factors that contribute to the disproportionate occurrence of pregnancy complications in minority women. It is clear that maternal stress can alter pregnancy outcome, although these effects are currently not well- understood. This project tests the hypothesis that high prenatal stress increases production of proinflammatory cytokines in pregnant women in a manner which contributes to poor pregnancy outcomes. We will use a prospective approach to assess stress, social support and cytokine production throughout pregnancy to see if these changes are predictive of poor outcome in a large, multi-ethnic sample. [unreadable] [unreadable] [unreadable]